Field of the Invention
The present invention relates to the field of in vivo fluorescence-based optical imaging of lumen-forming structures such as blood vessels, bile ducts, etc. using near infrared emission in the NIR-II range and further to the use of nanostructures such as carbon nanotubes, quantum dots, etc. solubilized for in vivo use.
Related Art
Presented below is background information on certain aspects of the present invention as they may relate to technical features referred to in the detailed description, but not necessarily described in detail. The discussion below should not be construed as an admission as to the relevance of the information to the claimed invention or the prior art effect of the material described.
Development of new therapies for peripheral arterial diseases (PADs) may be facilitated by imaging that provides anatomic and hemodynamic information with high spatial and temporal resolution. However, current methods for assessing vasculature and hemodynamics in small vessels in vivo are suboptimal. For imaging vascular structures, microscopic computed tomography (micro-CT) and magnetic resonance imaging (MRI) can resolve features down to ˜100 μm with deep penetration, but are limited by long scanning and post-processing time and difficulties in assessing vascular hemodynamics. On the other hand, vascular hemodynamics are usually obtained by Doppler measurements of micro-ultrasonography with high temporal resolution of up to 1000 Hz, but spatial resolution attenuates with increased depth of penetration.
In vivo fluorescence-based optical imaging has inherent advantages over tomographic imaging owing to high temporal and spatial resolution. Single-walled carbon nanotubes (SWNTs), nanoscale cylinders of rolled-up graphite sheets comprised of carbon, are an emerging nanomaterial with unique optical properties for in vivo anatomical imaging, tumor detection and photothermal treatment. One unique feature of SWNTs is their intrinsic fluorescence in the second near-infrared (NIR-II, 1.1-1.4 μm) window upon excitation in the traditional near-infrared region (NIR-I, 0.75-0.9 μm) with large Stokes shift up to ˜400 nm. Compared to the NIR-I window that has been extensively explored for in vitro and in vivo imaging, the longer wavelength emission in NIR-II makes SWNTs advantageous for imaging owing to reduced photon absorption and scattering by tissues, negligible tissue autofluorescence and thus deeper tissue penetration, allowing for unprecedented fluorescence-based imaging resolution of anatomical features deep to the skin.
Current methodologies for physiological imaging of PADs are suboptimal in that no single modality provides adequate spatial and temporal resolution to accurately assess all critical parameters, i.e. vascular structure, arterial inflow, venous outflow, and tissue perfusion. NIR-II imaging technique simultaneously provides anatomical and hemodynamic information and surpasses the need to use multiple imaging modalities to obtain equivalent data, owing to reduced tissue scattering and deeper anatomical penetration of NIR-II over shorter wavelengths. This is due to the inverse wavelength dependence (˜λ-1.1) of photon scattering as they travel through subcutaneous tissue and skin.
In addition, one of the issues of NIR-II imaging remains the limited choices of NIR-II fluorophores such as single-walled carbon nanotubes (SWNTs), certain types of quantum dots (QDs), and a handful of polymethine dyes. Other issues of NIR-II fluorophores include the relatively low fluorescence quantum yields and poor biocompatibility, which limit their use for in vivo imaging with enough temporal resolution. Currently, there is an urgent need for brightly fluorescent and biocompatible NIR-II fluorescent probes for biological imaging both in vitro and in vivo.